It is well known in biochemistry that all amino acids exist in two three dimensional forms, which are virtual mirror images of each other. The two forms are referred to in the art by the direction in which they rotate polarized light-levorotatory (L) and dextrorotatory (D), respectively left and right. Fischer representations of the structural formulas for the two enantiomers of glutamic acid are depicted below. 
It is also well known that the L-enantiomer is the naturally occurring form of each amino acid found in nature. The L-enantiomer of each amino acid that forms a part of a drug agent is also the “active” enantiomer for medicinal purposes.
It is well known that antifolates which contain only the L-enantiomer of glutamic acid are much more active than those which include the D-enantiomer in a racemic mixture of the two enantiomers. The pure D-enantiomer of MDAM, as with most antifolates, is virtually inactive as a drug.
4′-methylene-4-[(2,4-diamino-3,4-dihydropteridin-6-yl)ethyl]-benzoyl-glutamic acid, also referred to as 4-deoxy-4-amino-10-deazapteroyl-γ-methylene glutamic acid, and as γ-methylene-10-deazaaminopterin (MDAM) is a well-known investigational antitumor agent. MDAM is currently undergoing human clinical trials in the United States and abroad as a treatment for cancer. MDAM and other antifolates are essentially “two-part” molecules, with a pteroic acid part and an amino acid part. When L-γ-methylene-glutamic acid forms the amino acid part, the agent is known as L-MDAM.
γ-methylene-L-glutamic acid is also a well-known depolarizing agent in the rat spinal cord. This property is suggestive of potent CNS activity, which may translate into the development of agents to treat various CNS disorders.
γ-methylene-L-glutamic acid has been isolated in substantially pure form from germinated peanuts as described in U.S. Pat. No. 5,550,128. The free acid form of γ-methylene-L-glutamic acid has been synthesized starting from L-pyroglutamic acid, as shown in the Ezquerra publication, appended to the Information Disclosure Sheet that accompanies this application.
γ-methylene-L-glutamic acid, which makes up the amino acid part of L-MDAM has been previously synthesized, through a previously unpublished process from a di-protected L-pyroglutamate starting material. The pyroglutamate is available commercially, and has also been synthesized by a previously unpublished process.